Study to Evaluate the Analgesic Efficacy of 28 Days' Oral Administration of AZD2066 Compared with Placebo in Patients with Painful Diabetic Neuropathy

Study identifier:D0475C00009

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase IIa, Double-Blind, Randomised, Parallel-Group, Multi-Centre Study to Evaluate the Analgesic Efficacy of 28 Days' Oral Administration of AZD2066 Compared with Placebo in Patients with Painful Diabetic Neuropathy

Medical condition

Pain, Diabetic Neuropathy

Phase

Phase 2

Healthy volunteers

Study drug

AZD2066, Placebo

Sex

All

Actual Enrollment

127

Study type

Interventional

Age

18 Years - 80 Years

Date

Study Start Date: 01 Feb 2009

Primary Completion Date: 01 Aug 2009

Study Completion Date: 01 Aug 2009

Study design

Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Nov 2012 by AstraZeneca Pharmaceuticals

Collaborators

anders.neijber@astrazeneca.com

Inclusion and exclusion criteria

Location

Reserach Site

BELLA VISTA, AR, United States

Location

Research Site

NATIONAL CITY, CA, United States

Location

Research Site

WALNUT CREEK, CA, United States

Location

Research Site

DELAND, FL, United States

Location

Research Site

ORLANDO, FL, United States

Location

Research Site

MADISONVILLE, KY, United States

Location

Research Site

HOUSTON, TX, United States

Location

Research Site

Clearwater, FL, United States

Arms	Assigned Interventions
Experimental: 1	Drug: AZD2066 Capsule, once daily, 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28.
Placebo Comparator: 2	Drug: Placebo Capsule, once daily

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This multicenter study was conducted between February 2009 and August 2009in the United States.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study consisted of a 42-day enrollment phase (including washout and baseline period), a 28-day treatment phase (10-day inpatient and 18-day outpatient) where patients were randomized to AZD2066 or placebo, and a 7-day follow-up phase. Patients randomized to treatment with AZD2066 received 12 mg from Days 1 to 4 and 18 mg from Days 5 to 28.

Reporting Groups

	Description
AZD2066	Capsule, once daily. 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28.
Placebo	Capsule, once daily

Participant Flow: Overall Study

	AZD2066	Placebo
STARTED	62	65
COMPLETED	48	55
NOT COMPLETED	14	10
Adverse Event	5	2
Study-specific discontinuation criteria	5	3
Withdrawal by Subject	2	1
Lack of Efficacy	1	1
Severe non-compliance to protocol	1	1
Intake of prohibited medication	0	1
Positive for HEP C	0	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
AZD2066	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28
Placebo	Capsule, once daily

Baseline Measures

	AZD2066	Placebo	Total
Number of Participants [units: Participants]	62	65	127
Age Continuous ^[1] [units: years] Mean ± Standard Deviation	59.2 ± 9.2	57.0 ± 8.7	58.1 ± 8.95
Gender, Male/Female ^[2] [units: participants]
Female	26	31	57
Male	36	34	70

Outcome Measures

1. Primary Outcome Measure: Change in mean numerical rating scale (NRS) score from baseline to last 5 days of treatment [ Time Frame: From baseline to day 28 ]

Measure Type	Primary
Measure Name	Change in mean numerical rating scale (NRS) score from baseline to last 5 days of treatment
Measure Description	Change of mean pain intensity from 5-day baseline to the last 5 days of treatment, measured twice daily with NRS (12 hours recall). Mean pain intensity for 5-day baseline period (evening Day -6 to moning Day-1) and mean pain intensity for last 5 days on treatment (ie, last dose day and the 4 preceding calendar days) was calculated based on the numerical rating scale (NRS)(0-10). 0=No pain, 10=Worst pain imaginable.
Time Frame	From baseline to day 28
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol population (PP)

Reporting Groups

	Description
AZD2066	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28
Placebo	Capsule, once daily

Measured Values

	AZD2066	Placebo
Number of Participants Analyzed [units:participants]	46	51
Change in mean numerical rating scale (NRS) score from baseline to last 5 days of treatment [units: Scores on a scale] Least Squares Mean (Standard Error)	-2.33 (0.37)	-2.52 (0.36)

No statistical analysis provided for Change in mean numerical rating scale (NRS) score from baseline to last 5 days of treatment

2. Secondary Outcome Measure: Daily Numerical Rating Scale (NRS) pain scores and change from baseline over time to Day 28. [ Time Frame: From baseline to 28 days ]

Measure Type	Secondary
Measure Name	Daily Numerical Rating Scale (NRS) pain scores and change from baseline over time to Day 28.
Measure Description	Mean pain intensity per day (mean of morning and evening NRS values) and change from baseline were calculated for each study day. Baseline value= mean pain intensity for the 5-day baseline period. NRS scale (0- 10) where 0= No pain and 10= Worst pain imaginable.
Time Frame	From baseline to 28 days
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol population (PP)

Reporting Groups

	Description
AZD2066	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28
Placebo	Capsule, once daily

Measured Values

	AZD2066	Placebo
Number of Participants Analyzed [units:participants]	46	51
Daily Numerical Rating Scale (NRS) pain scores and change from baseline over time to Day 28. [units: Scores on a scale] Mean (Standard Deviation)	-2.3 (2.2)	-2.5 (2.3)

No statistical analysis provided for Daily Numerical Rating Scale (NRS) pain scores and change from baseline over time to Day 28.

3. Secondary Outcome Measure: Number of patients with >=30% reduction from baseline in Numerical Rating Scale (NRS) pain intensity score at Day 28 [ Time Frame: 28 days ]

Measure Type	Secondary
Measure Name	Number of patients with >=30% reduction from baseline in Numerical Rating Scale (NRS) pain intensity score at Day 28
Measure Description	Pain intensity score reduction=(change from baseline at D28/baseline)100 Responder= pain intensity score reduction ≥30% (yes/no)? Responder rate= (no. of responders/total no. of patients)100
Time Frame	28 days
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol population (PP)

Reporting Groups

	Description
AZD2066	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28
Placebo	Capsule, once daily

Measured Values

	AZD2066	Placebo
Number of Participants Analyzed [units:participants]	46	51
Number of patients with >=30% reduction from baseline in Numerical Rating Scale (NRS) pain intensity score at Day 28 [units: Participants]	23	25

No statistical analysis provided for Number of patients with >=30% reduction from baseline in Numerical Rating Scale (NRS) pain intensity score at Day 28

4. Secondary Outcome Measure: Number of patients with >=50% reduction from baseline in Numerical Rating Scale (NRS) pain intensity score at Day 28 [ Time Frame: 28 days ]

Measure Type	Secondary
Measure Name	Number of patients with >=50% reduction from baseline in Numerical Rating Scale (NRS) pain intensity score at Day 28
Measure Description	Pain intensity score reduction= (change from baseline D28/baseline)100 Responder=pain intensity score reduction ≥50% (Yes/No)? Responder rate= (no. of responders/total no. of patients)100
Time Frame	28 days
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol population (PP)

Reporting Groups

	Description
AZD2066	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28
Placebo	Capsule, once daily

Measured Values

	AZD2066	Placebo
Number of Participants Analyzed [units:participants]	46	51
Number of patients with >=50% reduction from baseline in Numerical Rating Scale (NRS) pain intensity score at Day 28 [units: Participants]	15	15

No statistical analysis provided for Number of patients with >=50% reduction from baseline in Numerical Rating Scale (NRS) pain intensity score at Day 28

5. Secondary Outcome Measure: Number of patients with Patient Global Impression of Change (PGIC) score of at least “much improved” at Day 28. [ Time Frame: 28 days ]

Measure Type	Secondary
Measure Name	Number of patients with Patient Global Impression of Change (PGIC) score of at least “much improved” at Day 28.
Measure Description	Patient Global Impression of Change (PGIC) scale ranges from 1-7, where 1= Very much improved and 7= Very much worse. Responder= Patient with a response of "much improved" or "very much improved" Responder rate= (no. of responders/total no. of patients)*100
Time Frame	28 days
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol population (PP)

Reporting Groups

	Description
AZD2066	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28
Placebo	Capsule, once daily

Measured Values

	AZD2066	Placebo
Number of Participants Analyzed [units:participants]	46	51
Number of patients with Patient Global Impression of Change (PGIC) score of at least “much improved” at Day 28. [units: Participants]	20	28

No statistical analysis provided for Number of patients with Patient Global Impression of Change (PGIC) score of at least “much improved” at Day 28.

6. Secondary Outcome Measure: Change in McGill Pain Questionnaire Short Form (MPQ-SF) Sensory Index from baseline to Day 28. [ Time Frame: From baseline to day 28. ]

Measure Type	Secondary
Measure Name	Change in McGill Pain Questionnaire Short Form (MPQ-SF) Sensory Index from baseline to Day 28.
Measure Description	Sensory index= sum of the intensity scale values of the words chosen for the descriptors 1-11 in the questionnaire. Range of scores for the sensory index= 0-33 (higher score represents a worse condition). Change from baseline (measured prior to randomization) to Day 28 was calculated.
Time Frame	From baseline to day 28.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol population (PP)

Reporting Groups

	Description
AZD2066	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28
Placebo	Capsule, once daily

Measured Values

	AZD2066	Placebo
Number of Participants Analyzed [units:participants]	46	51
Change in McGill Pain Questionnaire Short Form (MPQ-SF) Sensory Index from baseline to Day 28. [units: Scores on a scale] Least Squares Mean (Standard Error)	-6.87 (0.93)	-7.68 (0.88)

No statistical analysis provided for Change in McGill Pain Questionnaire Short Form (MPQ-SF) Sensory Index from baseline to Day 28.

7. Secondary Outcome Measure: Change in McGill Pain Questionnaire Short Form (MPQ-SF) Affective Index from baseline to Day 28. [ Time Frame: From baseline to day 28. ]

Measure Type	Secondary
Measure Name	Change in McGill Pain Questionnaire Short Form (MPQ-SF) Affective Index from baseline to Day 28.
Measure Description	Affective index= sum of the intensity scale values of the words chosen for the descriptors 12-15 in the questionnaire. Range of scores for the affective index=0-12 (higher score represents a worse condition). Change from baseline (measured prior to randomization) to Day 28 was calculated.
Time Frame	From baseline to day 28.
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol population (PP)

Reporting Groups

	Description
AZD2066	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28
Placebo	Capsule, once daily

Measured Values

	AZD2066	Placebo
Number of Participants Analyzed [units:participants]	46	51
Change in McGill Pain Questionnaire Short Form (MPQ-SF) Affective Index from baseline to Day 28. [units: Scores on a scale] Least Squares Mean (Standard Error)	-1.87 (0.35)	-2.06 (0.34)

No statistical analysis provided for Change in McGill Pain Questionnaire Short Form (MPQ-SF) Affective Index from baseline to Day 28.

8. Secondary Outcome Measure: Change in Brief Pain Inventory-Short Form (BPI-SF) pain severity from baseline to Day 28. [ Time Frame: From baseline to day 28.. ]

Measure Type	Secondary
Measure Name	Change in Brief Pain Inventory-Short Form (BPI-SF) pain severity from baseline to Day 28.
Measure Description	Change from baseline (measured prior to randomization) to Day 28 was calculated for the pain severity (mean of 4 intensity items). Each intensity item is recorded on a Numerical rating Scale (NRS) 0-10, where 0=No pain and 10= The worst pain.
Time Frame	From baseline to day 28..
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol population (PP)

Reporting Groups

	Description
AZD2066	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28
Placebo	Capsule, once daily

Measured Values

	AZD2066	Placebo
Number of Participants Analyzed [units:participants]	46	51
Change in Brief Pain Inventory-Short Form (BPI-SF) pain severity from baseline to Day 28. [units: Scores on a scale] Least Squares Mean (Standard Error)	-1.99 (0.35)	-2.19 (0.34)

No statistical analysis provided for Change in Brief Pain Inventory-Short Form (BPI-SF) pain severity from baseline to Day 28.

9. Secondary Outcome Measure: Change in Brief Pain Inventory-Short Form (BPI-SF) pain interference from baseline to Day 28. [ Time Frame: From baseline to 28 days ]

Measure Type	Secondary
Measure Name	Change in Brief Pain Inventory-Short Form (BPI-SF) pain interference from baseline to Day 28.
Measure Description	Change from baseline (measured prior to randomization) to Day 28 was calculated for pain interference (mean of 7 interference items). Each interference item is recorded on a Numerical Rating Scale (NRS 0-10), where 0= No interference and 10= Interferes completely.
Time Frame	From baseline to 28 days
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol population (PP)

Reporting Groups

	Description
AZD2066	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28
Placebo	Capsule, once daily

Measured Values

	AZD2066	Placebo
Number of Participants Analyzed [units:participants]	46	51
Change in Brief Pain Inventory-Short Form (BPI-SF) pain interference from baseline to Day 28. [units: Scores on a scale] Least Squares Mean (Standard Error)	-2.13 (0.31)	-2.13 (0.30)

No statistical analysis provided for Change in Brief Pain Inventory-Short Form (BPI-SF) pain interference from baseline to Day 28.

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
AZD2066	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28
Placebo	Capsule, once daily

Serious Adverse Events

AZD2066

Placebo

Total, serious adverse events

# participants affected / at risk

1/62 (1.61%)

1/65 (1.54%)

Injury, poisoning and procedural complications

Hip fracture¹

# participants affected / at risk

1/62 (1.61%)

0/65 (0.00%)

Cardiac disorders

Cardiac failure congestive; Myocardial infarction¹

# participants affected / at risk

0/62 (0.00%)

1/65 (1.54%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.0
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
AZD2066	Capsule, once daily 12 mg AZD2066 day 1-4 and 18 mg AZD2066 day 5-28
Placebo	Capsule, once daily

Other Adverse Events

AZD2066

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

19/62 (30.65%)

20/65 (30.77%)

Nervous system disorders

Headache¹

# participants affected / at risk

9/62 (14.52%)

11/65 (16.92%)

Nervous system disorders

Dizziness¹

# participants affected / at risk

7/62 (11.29%)

4/65 (6.15%)

Gastrointestinal disorders

Diarrhea¹

# participants affected / at risk

5/62 (8.06%)

6/65 (9.23%)

Musculoskeletal and connective tissue disorders

Arthralgia¹

# participants affected / at risk

4/62 (6.45%)

2/65 (3.08%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.0
2	Term from vocabulary,

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Gerard Lynch
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

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Download
CSR-D0475C00009.pdf
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Trial Results Summaries
Available here

Contacts

Contact

Quintiles Worldwide

clinical.studies.ns@quintiles.com

Investigators

Principal Investigator

Biljana Lilja

AstraZeneca R&D Södertälje151 85 Södertälje, Sweden

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Reserach Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=228&filename=CSR-D0475C00009.pdf

CSR-D0475C00009.pdf

Trial Results Summaries